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Caffeine is the most widely used drug in the world and acts mainly through antagonism of the effects mediated by the adenosine receptor subtypes A1, A2A, A2B and A3. We determined whether repeated caffeine administration at different doses and for different periods of time (400 or 600 mg/day for 1 week and 400 mg/day for 2 weeks) alters human neutrophil A2A adenosine receptor density and function. Saturation binding assays showed an increase in affinity (KD) and density (Bmax) of A2A adenosine receptors after caffeine intake. These changes were accompanied by increases in cAMP accumulation and decreases in superoxide anion production after stimulation of the A2A receptor subtype using the agonist 5′-N-ethylcarboxamidoadenosine (NECA). Binding and functional changes of A2A receptors returned to baseline after 48 h of caffeine withdrawal. The findings are consistent with a potential anti-inflammatory effect of caffeine mediated by neutrophil A2A receptors. [ABSTRACT FROM AUTHOR]

Mothers with hepatitis C virus (HCV) and HIV coinfection are the major source of HCV/HIV coinfection in infancy and childhood. There is no known intervention capable of interrupting HCV spread from mother to child, while the majority of infant HIV infections occurring in the developed world can be prevented by antiretroviral prophylaxis in the mother and child, elective caesarean section, and formula-feeding. In the era preceding treatment of HIV infection with highly active antiretroviral therapy, HCV coinfection was of little concern because the short-term survival of patients with HIV infection prevented the slowly developing consequences of chronic hepatitis C. As the life expectancy of patients with HIV infection increased with therapy, HCV has emerged as a significant pathogen. Several lines of evidence in adult patients suggest that liver disease may be more severe in patients coinfected with HIV and that progression of HIV disease may be accelerated by HCV coinfection. Whether coinfected children may share these clinical patterns remains a matter of speculation. Chronic hepatitis C in otherwise healthy children is usually a mild disease; liver damage may be sustained and fibrosis may increase over the years, suggesting slow progression of the disease. Interferon-α has been the only drug used in the past decade to treat hepatitis C in children and adolescents, with average response rates of 20%. Preliminary results of treatment with interferon-α and ribavirin suggest that the efficacy would be greater with combined therapy. These treatment protocols have not yet been applied to children coinfected with HIV, but the increasing number of long-term survivors will probably prompt further investigation in the near future. At present, treating HIV disease and monitoring HCV infection and hepatotoxicity induced by antiretroviral drugs seem to be the more reasonable approach to HCV/HIV coinfection in childhood. [ABSTRACT FROM AUTHOR]

This prospective multicenter study evaluated separately the significance of maternal injection drug use (IDU) and human immunodeficiency virus type 1 (HIV-1) coinfection in vertical transmission of hepatitis C virus (HCV). In all, 1372 consecutive, unselected HCV antibody-positive mothers and their infants were studied. Maternal HIV-1 coinfection (crude odds ratios [OR], 1.41; 95% confidence interval [CI], 1.16-1.66; P =.007) and IDU (OR, 1.58; 95% CI, 1.37-1.78; P <.00001) were linked to mother-to-child HCV transmission in unadjusted analysis when all anti-HCV-positive mothers were evaluated. When only HCV RNA-positive mothers were evaluated, maternal IDU, but not maternal HIV-1 coinfection, was significantly associated with mother-to-child HCV transmission. Multivariable analysis confirmed the link between maternal IDU and HCV transmission (adjusted OR [AOR], 1.51; 95% CI, 1.19-1.92; P =.0006), but no association was found with HIV-1 coinfection (AOR, 0.98; 95% CI, 0.73-1.33; P =.93). IDU, but not HIV-1 coinfection, seems to be a preeminent risk factor for vertical HCV transmission. © 2002 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

ABSTRACT- During a prospective follow-up study of 65 children with chronic hepatitis B, the HBcAg expression pattern in the liver was investigated, by immunofluorescence, in relation to biochemical and histological features and to the evolution of the disease. HBcAg was detected in 50 (77%) cases, with a diffuse pattern of distribution (more than 60% positive nuclei) in 20 cases, and with a focal pattern (less than 40% positive nuclei) in 30 cases. The diffuse pattern significantly prevailed in younger children, while the focal pattern was more frequent in children beyond 10 years of age. Transaminase levels were higher and histological features of activity were more frequent in patients with the focal pattern than in those with a diffuse pattern. Twenty-five hepatitis B e antigen (HBeAg) positive children, all initially HBcAg positive, were followed prospectively for 24 months. Seroconversion to anti-HBe, with subsequent normalization of transaminases, occurred in 72% of cases with a focal pattern, but only in 21% of those with a diffuse HBcAg pattern. In four patients transition from the diffuse to the focal pattern was observed during follow-up. These results suggest that, in children with chronic hepatitis B, the diffuse HBcAg pattern in the liver might reflect an earlier phase of infection. In HBeAg positive cases the focal HBcAg pattern may represent a prognostic marker of short-term favourable evolution of the disease. [ABSTRACT FROM AUTHOR]

ABSTRACT- An antigen-antibody system has been identified by immunofluorescence in patients with non-A, non-B hepatitis. The non-A, non-B antigen was localized in the hepatocyte nuclei of liver biopsies from patients with acute post-transfusion or sporadic non-A, non-B hepatitis and in those from patients with chronic post-transfusion non-A, non-B hepatitis, the percentage of positive cells being most prominent in patients receiving immunosuppressive treatment. Absence of the antigen in normal livers and in livers from patients with type B hepatitis infection indicated its specific association with non-A, non-B infection. Antibody reacting with the nuclear antigen became detectable in serum during post-transfusion acute non-A, non-B hepatitis in 11 out of 15 cases; it was absent before transfusion. Six out of 12 cases of sporadic acute non-A, non-B hepatitis were also found to produce the antibody, which was repeatedly found to be absent during the acute phase in five patients with type A and in eight with type B hepatitis. The non-A, non-B antibody, mainly an IgM antibody, persisted in serum for prolonged periods of time after onset, both in patients showing biochemical resolution of their illness and in those who continued to have liver damage after the acute phase. Accordingly, eight out of nine patients withchronic non-A, non-B hepatitis were found positive for the antibody in serum, seven at the time the non-A, non-B antigen was detected in their liver. Thus this non-A, non-B associated antigen-antibody system shares remarkable similarities of behaviour with the 'core' system of the hepatitis B virus. [ABSTRACT FROM AUTHOR]

Epidemiological and clinical features of acute symptomatic hepatitis type B were evaluated in 51 otherwise healthy children and in 13 children receiving immunosuppressive treatment for leukaemia and malignancy, who were admitted to hospital with acute hepatitis B surface antigen (HBsAg) positive hepatitis during a period of 7 years. Blood transfusions, or intimate contacts with asymptomatic HBsAg carriers or with contaminated material during repeated admission to hospital were the possible sources of infection in the immunosuppressed patients, whereas percutaneous exposure was identified as the source in a minority of non-immunosuppressed patients. Features of the acute phase of the illness differed little between the two groups of patients (acute liver failure developed in one patient with leukaemia and in two untreated children). Conversely, chronic evolution was observed in 69% of immunosuppressed patients but in only 9% of untreated children and affected only patients born to HBsAg positive mothers (two of four patients) or patients presenting with papular acrodermatitis (both patients). [ABSTRACT FROM AUTHOR]

During a multicentre study of chronic hepatitis in childhood diagnosed by biopsy, the spectrum of the disease has been evaluated in 196 consecutive patients, including 157 from Northern Italy and 39 from Southern Italy. Only 31% of patients in the former group and 27% in the latter were symptomatic when first seen: the majority of cases being seen after familial screenings for hepatitis B virus (HBV) markers or during intercurrent infections, thus suggesting that the frequency of chronic hepatitis in childhood might be largely underestimated in our area. In Southern and Northern Italy 83% of symptomatic and 95% of asymptomatic patients were hepatitis B surface antigen (HBsAg) positive in serum; only 15 (8.3%) of these children were born to mothers known to be HBsAg positive at delivery, but a high circulation of HBV was found in their families: in fact more than 65% of household contacts in Northern Italy and more than 90% in Southern Italy had serological evidence of past or ongoing HBV infection. These data indicate that, although familial screenings for HBV could have enhanced the percentage of HBsAg positive asymptomatic cases, chronic hepatitis in Italian children is mainly caused by HBV infection acquired in the familial setting through horizontal transmission. Such findings also emphasise the importance of mass vaccination of infants as the most effective means to prevent chronic type B hepatitis in childhood in our area. Among HBsAg positive children 55% had histological features of chronic active hepatitis and 85% were hepatitis Be antigen (HBeAg) positive in serum. Anti-HBe positive hepatitis was significantly more frequent in Southern than in Northern Italy in parallel with the significantly higher prevalence (17%) of hepatitis delta virus infection in that area. Of the 16 HBsAg negative cases included in the study three had autoimmune hepatitis, three Wilson's disease, one alpha1 antitrypsin deficiency, and nine had cryptogenic hepatitis, often associated to mild liver lesions resembling those seen in our adult patients with chronic non-A, non-B hepatitis unrelated to percutaneous exposure. [ABSTRACT FROM PUBLISHER]

Serological evidence of infection with the hepatitis B virus associated delta agent (delta) was found in 34 of 270 Italian children with HBsAg-positive liver disease. In different histological forms of chronic HBsAg hepatitis the prevalence of delta infection increased in parallel with the activity of the disease and was maximal in children with cirrhosis. During two to seven years of follow up the hepatitis deteriorated in 38% of the 34 patients with delta infection and ameliorated only in 9%. By contrast the disease usually ran a mild course in the 236 delta-negative carriers of HBsAg, with remission in 55% of these children and deterioration in only 7%. The outcome of chronic hepatitis associated with delta infection was not influenced by treatment with steroids and azathioprine. Chronic delta infection in children is usually accompanied by serious liver disease, that has a tendency to progress and is unresponsive to conventional immunosuppressive treatment. [ABSTRACT FROM PUBLISHER]

Clinical, virological, and histological features of hepatitis B virus infection have been examined in 35 children, aged 1 to 11 years, known to be hepatitis B surface antigen (HBsAg) carriers for at least six months when entering the study. Only 10 patients had a history of acute unresolved hepatitis: in the remaining cases the detection of HBsAg had been an occasional finding. Although 77% of the patients were asymptomatic, all had evidence of hepatic involvement and liver history showed the features of chronic persistent hepatitis in 18 cases and of chronic active hepatitis in 16 cases, with associated cirrhosis in two of them. One patient had only minimal histological changes. A high percentage of children with both chronic persistent and chronic active hepatitis had evidence of active virus replication throughout the observation period. During the follow-up study of one to eight years (mean 3.1 +/- 1.7 years), transaminase levels became consistently normal in five patients with chronic persistent hepatitis, and inflammatory infiltrates disappeared in three of them. However, only one of these children cleared HBsAg from serum. Eleven of 16 patients with chronic active hepatitis received immunosuppressive treatment but only one of them achieved a complete and protracted remission, although active viral replication persisted. On the other hand, two of five untreated patients reached complete remission after two and three years of follow-up respectively and one of them cleared HBsAg three years later. These results would suggest the possibility of a spontaneous complete remission of HBsAg positive chronic active hepatitis in children but also raise doubts about the usefulness of immunosuppressive therapy in such patients. [ABSTRACT FROM PUBLISHER]

The cytotoxic effect of peripheral lymphocytes on chicken red blood cells (ChRBC) coated with purified hepatitis B surface antigen (HBsAg) has been studied as an parameter of cell-mediated immunity in acute and chronic infection with hepatitis B virus. Using this technique, the mean cytotoxic index of lymphocytes from patients with acute hepatitis B (29·13 ± 20·88) was significantly higher than that obtained with lymphocytes from control subjects (6·53 ± 3·75). Only 33·3% of the patients with HBsAg-positive chronic active hepatitis exhibited lymphocyte cytotoxicity to HBsAg-coated target cells and the mean cytotoxic index (11·66 ± 6·60) was in these cases significantly lower than that found in acute hepatitis B. Healthy chronic carriers of HBsAg failed to show lymphocyte cytotoxicity to target cells. The effector cells detected in acute hepatitis B by this assay have been demonstrated to be T-lymphocytes, as T-cell depleted subpopulations lacked cytotoxic activity. Target cell lysis could be blocked by addition of HBsAg-coated unlabelled ChRBC as well as of purified HBsAg in the culture tubes. It is suggested that damage to the liver cells in acute hepatitis B is related to the presence of cytotoxic T-lymphocytes reacting with HBsAg on the surface of infected hepatocytes. An inadequate lymphocyte response to the antigen may be responsible for the persistence of the infection in the liver with varied clinical manifestations and associated hepatic lesions. [ABSTRACT FROM PUBLISHER]

The authors of the paper "Fatal cardiac air embolism after CT-guided percutaneous needle lung biopsy: medical complication or medical malpractice?" respond to a commentary by Dr. Wingren. While Dr. Wingren suggests that the manner of death cannot be determined based on autopsy findings and clinical records, the authors argue that there is evidence to suggest that the event was due to a fistula between an air-containing space and vessels, rather than medical malpractice. They emphasize the importance of adhering to guidelines and using logical scientific reasoning when assessing cases of medical liability. The authors also suggest the application of Bayes' theorem to support the justice system in a more efficient and transparent manner. [Extracted from the article]